Fas activity mediates airway inflammation during mouse adenovirus type 1 respiratory infection

• Published in: Virology (New York, N.Y.) Vol. 521; pp. 129 - 137
• Main Authors: Adkins, Laura J., Molloy, Caitlyn T., Weinberg, Jason B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2018
• Subjects: Adenoviridae Infections - physiopathology; Adenovirus; Animals; CD8 T cells; CD8-Positive T-Lymphocytes - immunology; Cytokines - biosynthesis; Disease Models, Animal; Fas; Fas Ligand Protein - metabolism; fas Receptor - deficiency; fas Receptor - metabolism; Gene Expression Profiling; Histocytochemistry; Immunohistochemistry; Inflammation - physiopathology; Lung - pathology; Mice; Mice, Inbred C57BL; Real-Time Polymerase Chain Reaction; Respiratory infection; Respiratory Tract Infections - physiopathology; RNA, Messenger - analysis; Viral Load; Fas; Adenovirus; Respiratory infection; CD8 T cells
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2018.06.002

CD8 T cells play a key role in clearance of mouse adenovirus type 1 (MAV-1) from the lung and contribute to virus-induced airway inflammation. We tested the hypothesis that interactions between Fas ligand (FasL) and Fas mediate the antiviral and proinflammatory effects of CD8 T cells. FasL and Fas expression were increased in the lungs of C57BL/6 (B6) mice during MAV-1 respiratory infection. Viral replication and weight loss were similar in B6 and Fas-deficient (lpr) mice. Histological evidence of pulmonary inflammation was similar in B6 and lpr mice, but lung mRNA levels and airway proinflammatory cytokine concentrations were lower in MAV-1-infected lpr mice compared to infected B6 mice. Virus-induced apoptosis in lungs was not affected by Fas deficiency. Our results suggest that the proinflammatory effects of CD8 T cells during MAV-1 infection are mediated in part by Fas activation and are distinct from CD8 T cell antiviral functions.
•Fas and Fas ligand expression increases in the lungs of MAV-1-infected mice.•Fas deficiency does not impair control of MAV-1 replication in the lungs.•Proinflammatory cytokine production is decreased in airways of Fas-deficient mice.